The proposal is designed to investigate three major areas of cellular iron metabolism in erythroid cells and hepatocytes: 1) Transferrin Receptors. Studies of the interaction of transferrin, the plasma carrier of iron, with specific receptors on the cell plasma membrane. 2) Plasma Membrane Iron Binding Proteins. Characterization and isolation of those membranes proteins which accept iron from transferrin. 3) Cytosol Transport of Iron. Characterization and isolation of cytosol components which carry iron from the plasma membrane to mitochondria for insertion into heme. These aspects on iron metabolism also will be investigated in disordered states of iron metabolism including iron deficiency and iron oveload. The various moieties involved in iron transport will be incorporated into liposomes to allow reconstitution of the iron transport system with subsequent step-by-step analysis using purified components.